In 2014, the U.S. Food and Drug Administration launched its first youth smoking prevention media campaign, "The Real Cost," with the goal of preventing cigarette smoking among at-risk youth aged 12-17 years in the U.S. This paper examines how the paid media strategy was developed, implemented, and refined between 2013 and 2016. Specifically, this paper discusses how research and best practices informed the media targeting strategy used to implement a multifaceted national campaign that successfully reached and influenced thousands of teens at risk for cigarette smoking. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Fifth Anniversary Retrospective of "The Real Cost," the Food and Drug Administration's Historic Youth Smoking Prevention Media Campaign, which is sponsored by the U.S. Food and Drug Administration.

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